The predictive value of serum p-CREB level on secondary cognitive impairment in patients with mild-to-moderate craniocerebral trauma

  • Chenyang Han
  • Yi Yang
  • Shuiliang Ruan
  • Li Guo
  • Xiaoling Zhang
  • Qiaobing Guan
Original Article


The study was designed to investigate the predictive value of phosphorylated CAMP response element binding protein (p-CREB) level in peripheral blood on secondary cognitive impairment in patients with mild-to-moderate craniocerebral trauma. A total of 107 patients with mild-to-moderate craniocerebral trauma were selected, who were admitted to the Second Affiliated Hospital of College of Jiaxing from January 2016 to January 2017. Of them, 30 patients were diagnosed with secondary mild cognitive impairment (MCI) during follow-up, who were assigned to the experimental group. The remaining 77 subjects were assigned to the control group, without significant cognitive impairment. The clinical data of patients were compared between two groups, and the clinical data of patients with different p-CREB levels were compared. Logistic regression analysis was used to investigate the risks of MCI in patients with different p-CREB levels. Moreover, multiple linear regression analysis was employed to assess the influencing factors of scores of Mini-Mental State Examination (MMSE) on patients with secondary MCI. The following pathophysiologic factors, including age, rescuing time, the proportion of hypertension, trauma severity score (AIS-ISS), and serum total cholesterol (TC) were significantly higher in patients in the experimental group compared to those in the control group (all P < 0.05). The serum level of p-CREB ranged from 0.127 to 1.852 ng/ml. Afterwards, the serum levels of p-CREB of patients were divided into four quartiles. The first, second, third, and fourth quartile groups were 0.127–0.548 ng/ml, 0.549–0.982 ng/ml, 0.983–1.412 ng/ml, and 1.413–1.852 ng/ml, respectively. As the level of p-CREB increased, age, rescuing time, the proportion of hypertension, and AIS-ISS gradually decreased, with statistical significance (all P < 0.05). Univariate and multivariate logistic regression analyses demonstrated that the risk of secondary MCI of patients in the first quartile was 1.21 and 1.58 times of the fourth quarter, respectively. Multivariate linear regression analysis showed that age, rescuing time, AIS-ISS, and serum p-CREB level were independent influencing factors of MMSE score in secondary MCI patients. For each increase of 0.1 ng/ml in serum p-CREB level, the MMSE score increased by 0.382 in MCI patients. Serum p-CREB level was an independent risk factor of secondary MCI in patients with mild-to-moderate craniocerebral trauma, whose level was significantly correlated with the injured degree of cognitive impairment. The level of p-CREB is also age-related, and younger patients have a higher level.


Cognitive impairment p-CREB Craniocerebral trauma Secondary 


Compliance with ethical standards

Ethical standards

This study conforms to the relevant ethical regulations, and the research program and process are approved by the Ethics Committee. All patients voluntarily participated and signed the informed consent.


  1. 1.
    Moscote-Salazar L, Satyarthee G, Matus J et al (2017) Late-onset development of tachylalia following a closed traumatic craniocerebral injury associated with bitemporal gliosis. J Med Sci 3(3):159–165Google Scholar
  2. 2.
    Feinkohl I, Winterer G, Spies CD, Pischon T (2017) Cognitive reserve and the risk of postoperative cognitive dysfunction. Dtsch Arztebl Int 114(7):110–118Google Scholar
  3. 3.
    Hardigan T, Ward R, Ergul A (2016) Cerebrovascular complications of diabetes: focus on cognitive dysfunction. Clin Sci 130(20):1807–1822CrossRefGoogle Scholar
  4. 4.
    Li X, Guo C, Li Y, Li L, Wang Y, Zhang Y, Li Y, Chen Y, Liu W, Gao L (2017) Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway. Oncotarget 8(20):32433–32449Google Scholar
  5. 5.
    Jiang T, Wang XQ, Ding C et al (2017) Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling. Korean J Physiol Pharmacol 21(6):579–589CrossRefGoogle Scholar
  6. 6.
    Yin JCP, Wallach JS, Vecchio MD et al (1994) Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79(1):49–58CrossRefGoogle Scholar
  7. 7.
    Salottolo K, Settell A, Uribe P, Akin S, Slone DS, O'Neal E, Mains C, Bar-Or D (2009) The impact of the AIS 2005 revision on trauma severity scores and clinical outcome measures. Trauma-international Journal of the Care of the Injured 40(9):999–1003Google Scholar
  8. 8.
    Jacinto AF, Brucki SMD, Porto CS et al (2014) Subjective memory complaints in the elderly: a sign of cognitive impairment? Clinics 69(3):194–197CrossRefGoogle Scholar
  9. 9.
    Zhengdong L, Donghua Z, Jianhua Z et al (2015) Use of 3D reconstruction of emergency and postoperative craniocerebral CT images to explore craniocerebral trauma mechanism. Forensic Sci Int 255:106–111CrossRefGoogle Scholar
  10. 10.
    Chrivia JC, Kwok RP, Lamb N et al (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365(6449):855–859CrossRefGoogle Scholar
  11. 11.
    Walters CL, Kuo YC, Blendy JA (2003) Differential distribution of CREB in the mesolimbic dopamine reward pathway. J Neurochem 87(5):1237–1244CrossRefGoogle Scholar
  12. 12.
    Barresi V, Mondello S, Branca G, Rajan TS, Vitarelli E, Tuccari G (2015) p-CREB expression in human gliomas: potential use in the differential diagnosis between astrocytoma and oligodendroglioma. Hum Pathol 46(2):231–238CrossRefGoogle Scholar
  13. 13.
    Hayward P (2004) Presenilin dysfunction leads to memory and plasticity defects. Lancet Neurol 3(6):327–331CrossRefGoogle Scholar
  14. 14.
    Sekeres M J, Sargin D, Ross P J et al (2015) The role of CREB and CREB co-activators in memory formation. In: Memory Mechanisms in Health and Disease: Mechanistic Basis of Memory 15(11):171–194Google Scholar
  15. 15.
    Sukiasyan SG, Tadevosyan MY (2015) The role of craniocerebral trauma in the dynamics of combat-related post-traumatic stress disorder. Neurosci Behav Physiol 45(9):1086–1094CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyThe Second Affiliated Hospital of Jiaxing UniversityJiaxingChina
  2. 2.Department of neurosurgeryThe Second Affiliated Hospital of Jiaxing UniversityJiaxingChina
  3. 3.Department of Center LaboratoryThe Second Affiliated Hospital of Jiaxing UniversityJiaxingChina
  4. 4.Department of NeurologyThe Second Affiliated Hospital of Jiaxing UniversityJiaxingChina

Personalised recommendations